Genetic studies of human cell DNA repair and carcinogenesis have been initiated by protoplast fusion transfection of a variety of types of human cells with specific cellular and viral genes known to play a role in human carcinogenesis. The role of the ras gene in normal human bronchial epithelial cell carcinogenesis is being studies by analyzing the progression of Harvey murine sarcoma virus (v-Ha-ras) transfected HBE cells through the states of resistance to squamous cell differentiation, immortalization, anchorage independent growth, tumorigenicity and metastasis in athymic nude mice. The advantage of genetic transfection vis-a-vis virus/helper-virus experiments to study the biological activities of viral genes includes the ability to produce virus-free human cell lines that stably carry and express virus gene products. This circumvents the bio-hazards associated with virus shedding cell cultures and the technical problems of human cells releasing transforming viruses during xenotransplantation experiments testing the tumorigenicity of transformed human cells. Characterization of v-Ha-ras-transfected human bronchial epithelial cells, including restriction mapping of transfection loci, selection of tumorigenic and nontumorigenic clones, and determination of conditions required for expression of tumorigenic phenotypes will provide information to elucidate the mechanism of ras-mediated carcinogenesis in an important progenitor cell of human lung cancer.